8fca - Revision history

OCA at 06:42, 19 June 2024

2024-06-19T06:42:30Z

← Older revision		Revision as of 06:42, 19 June 2024
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/TRPV4_HUMAN TRPV4_HUMAN] Non-selective calcium permeant cation channel probably involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by low pH, citrate and phorbol esters. Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism. Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers. Acts as a regulator of intracellular Ca(2+) in synoviocytes. Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8.<ref>PMID:11025659</ref> <ref>PMID:12724311</ref> <ref>PMID:19759329</ref>		[https://www.uniprot.org/uniprot/TRPV4_HUMAN TRPV4_HUMAN] Non-selective calcium permeant cation channel probably involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by low pH, citrate and phorbol esters. Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism. Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers. Acts as a regulator of intracellular Ca(2+) in synoviocytes. Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8.<ref>PMID:11025659</ref> <ref>PMID:12724311</ref> <ref>PMID:19759329</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Crosstalk between ion channels and small GTPases is critical during homeostasis and disease, but little is known about the structural underpinnings of these interactions. TRPV4 is a polymodal, calcium-permeable cation channel that has emerged as a potential therapeutic target in multiple conditions. Gain-of-function mutations also cause hereditary neuromuscular disease. Here, we present cryo-EM structures of human TRPV4 in complex with RhoA in the ligand-free, antagonist-bound closed, and agonist-bound open states. These structures reveal the mechanism of ligand-dependent TRPV4 gating. Channel activation is associated with rigid-body rotation of the intracellular ankyrin repeat domain, but state-dependent interaction with membrane-anchored RhoA constrains this movement. Notably, many residues at the TRPV4-RhoA interface are mutated in disease and perturbing this interface by introducing mutations into either TRPV4 or RhoA increases TRPV4 channel activity. Together, these results suggest that RhoA serves as an auxiliary subunit for TRPV4, regulating TRPV4-mediated calcium homeostasis and disruption of TRPV4-RhoA interactions can lead to TRPV4-related neuromuscular disease. These insights will help facilitate TRPV4 therapeutics development.

	TRPV4-Rho GTPase complex structures reveal mechanisms of gating and disease.,Kwon DH, Zhang F, McCray BA, Feng S, Kumar M, Sullivan JM, Im W, Sumner CJ, Lee SY Nat Commun. 2023 Jun 23;14(1):3732. doi: 10.1038/s41467-023-39345-0. PMID:37353484<ref>PMID:37353484</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 8fca" style="background-color:#fffaf0;"></div>~~
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:20, 12 July 2023

2023-07-12T07:20:48Z

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-The entry 8fca is ON HOLD
+==Cryo-EM structure of the human TRPV4 - RhoA in complex with 4alpha-Phorbol 12,13-didecanoate==
-Authors:
+TRPV4-Rho GTPase complex structures reveal mechanisms of gating and disease.,Kwon DH, Zhang F, McCray BA, Feng S, Kumar M, Sullivan JM, Im W, Sumner CJ, Lee SY Nat Commun. 2023 Jun 23;14(1):3732. doi: 10.1038/s41467-023-39345-0. PMID:37353484<ref>PMID:37353484</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>

OCA at 07:47, 19 April 2023

2023-04-19T07:47:23Z

← Older revision		Revision as of 07:47, 19 April 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8fca is ON HOLD ~~until Paper Publication~~		The entry 8fca is ON HOLD

	Authors:		Authors:

OCA at 05:07, 8 February 2023

2023-02-08T05:07:58Z

← Older revision		Revision as of 05:07, 8 February 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8fca is ON HOLD		The entry 8fca is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8fca" [edit=sysop:move=sysop]

2022-12-07T05:43:12Z

Protected "8fca" [edit=sysop:move=sysop]

← Older revision	Revision as of 05:43, 7 December 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8fca is ON HOLD Authors: Description: Category: Unreleased Structures

2022-12-07T05:43:08Z

New page: '''Unreleased structure''' The entry 8fca is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8fca is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]